Previous observations of variations in the acute insulin response suggested that this phenotype was controlled by one or more genes. Glucokinase, which has been linked to the MODY (maturity onset diabetes of the young) form of diabetes, has been proposed as an intracellular glucose sensor and appeared to be a likely candidate gene. Similarly, GLUT2, the major glucose transporter of the pancreas could also be responsible for the variation observed in the acute insulin response. Polymorphisms at both of these genes have been examined for linkage with the acute insulin response. In an analysis of 117 sibpairs linkage between this region on chromosome 3 and the acute insulin response could not be excluded. A structural analysis of the coding regions for the gene encoding GLUT2 revealed a single transition which predicts an amino acid substitution at position 110 of GLUT2. It is currently unknown how the mutation effects glucose sensing in the BETA-cell.